Molecular Interactions in the Eubacterial Replisome: a Paradigm for Study of Dynamic Macromolecular Machines

DNA replication in all organisms requires as many as 30 different proteins to interact in a structure called the replisome, a large molecular machine that pumps DNA through it as it simultaneously makes copies of both strands. In this project, we will develop a comprehensive structural model of the replisome in atomic detail, and define the chemical contacts that mediate dynamic protein-protein and protein-nucleic acid interactions in it, as a model system for study of other dynamic macromolecular assemblies. This will provide information to enable development of antibacterial agents that act by disrupting these interactions, and new chemistries for use in biosensors and diagnostic applications.